Project Summary/Abstract The applicant, Miriam Bredella MD, is a clinically active staff radiologist in the Division of Musculoskeletal Imaging and Interventions at the Massachusetts General Hospital and an Associate Professor of Radiology at Harvard Medical School. Over the last 11 years Dr. Bredella?s research has focused on advanced functional imaging techniques investigating mechanisms of bone loss in obesity. Her prior mentoring experience, publication and funding record together with her current and planned research support demonstrate her commitment and passion for patient-oriented research and provide an excellent foundation to accomplish the goals and objectives of the K24 Award. The specific aims addressing the purpose of the K24 Award are: 1) To enable Dr. Bredella to dedicate 50% of her time to mentor junior clinical investigators based on her already NIH funded R01 grant on bone metabolism in adolescents undergoing bariatric surgery; 2) To mentor junior clinical investigators from the Endocrine and Radiology Departments and other specialties interested in metabolic research, investigators from the T32 program in Nutrition and Metabolism, and the pool of residents and fellows in Endocrinology and Radiology with the goal to develop them into clinical researchers who can successfully compete for peer-reviewed grants related to the mission of the NIDDK; and 3) To enable Dr. Bredella to further establish a patient-oriented research program that combines innovative translational, clinical, and outcomes research in metabolic imaging and that provides an ideal environment to develop future leaders in clinical research. The training environment at the PI's institution is outstanding in terms of didactic resources and availability of techniques to assess complex metabolic endpoints. Importantly, Dr. Bredella enjoys strong commitment from the leadership of both Endocrinology and Radiology who have enthusiastically endorsed her successful mentoring efforts to date and the plans in the current proposal. The specific research aims of the application are based on the candidate?s successfully funded R01, investigating in morbidly obese adolescent boys and girls undergoing Roux-en-Y gastric bypass (RYGB) or vertical sleeve gastrectomy (VSG) 1) whether areal and volumetric BMD and strength estimates by finite element analysis (FEA) will decrease, and cortical and trabecular microarchitecture will be impaired whereas marrow adipose tissue (MAT) will increase and bone resorption markers will exceed those of bone formation markers and 2) investigating novel physiologic mechanisms mediating skeletal changes after RYGB and VSG. New directions proposed in the current application will estimate risk of fracture after RYGB and VSG by using a novel, biomechanically-based approach that encompasses both bone strength (by FEA) and skeletal loading (by musculoskeletal modeling), thereby accounting for extreme changes in body composition that influence fracture risk.